Dataset Information

Evolution of radiographic joint damage in rituximab-treated versus TNF-treated rheumatoid arthritis cases with inadequate response to TNF antagonists.

ABSTRACT:

Background

Observational studies have suggested that patients with rheumatoid arthritis (RA) who experience inadequate response to anti-tumour necrosis factor (anti-TNF) agents respond more favourably to rituximab (RTX) than to an alternative anti-TNF agent. However, the relative effectiveness of these agents on long-term outcomes, particularly in radiographic damage, remains unclear.

Objective

To compare the effectiveness of RTX against anti-TNF agents in preventing joint damage in patients with RA who have experienced inadequate response to at least one prior anti-TNF agent.

Methods

This is a prospective cohort study within the Swiss registry of patients with RA who discontinued at least one anti-TNF agent and subsequently received either RTX or an alternative anti-TNF agent. The primary outcome, progression of radiographic joint erosions (Ratingen erosion score)over time, and the secondary outcome, functional disability (Health Assessment Questionnaire Disability Index), were analysed using regression models for longitudinal data and adjusted for potential confounders.

Results

Of the 371 patients included, 104 received RTX and 267 received an alternative anti-TNF agent. During the 2.6-year median follow-up period, the rates of Ratingen erosion score progression were similar between patients taking RTX and patients taking an alternative anti-TNF agent (p=0.67). The evolution of the Health Assessment Questionnaire score was statistically significantly better in the RTX group (p=0.016), but the magnitude of the effect was probably not clinically relevant.

Conclusion

This observational study suggests that RTX is as effective as an alternative anti-TNF agent in preventing erosions in patients with RA who have previously experienced inadequate response to anti-TNF agents.

SUBMITTER: Finckh A

PROVIDER: S-EPMC3500530 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Publications

Evolution of radiographic joint damage in rituximab-treated versus TNF-treated rheumatoid arthritis cases with inadequate response to TNF antagonists.

Finckh Axel A Möller Burkhard B Dudler Jean J Walker Ulrich A UA Kyburz Diego D Gabay Cem C

Annals of the rheumatic diseases 20120314 10

<h4>Background</h4>Observational studies have suggested that patients with rheumatoid arthritis (RA) who experience inadequate response to anti-tumour necrosis factor (anti-TNF) agents respond more favourably to rituximab (RTX) than to an alternative anti-TNF agent. However, the relative effectiveness of these agents on long-term outcomes, particularly in radiographic damage, remains unclear.<h4>Objective</h4>To compare the effectiveness of RTX against anti-TNF agents in preventing joint damage ...[more]

PMID: 22419773

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Project description:OBJECTIVE:To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) ? inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis. DESIGN:Population based prospective study. SETTING:53 university and 54 non-university clinical centres in France. PARTICIPANTS:3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months. INTERVENTION:Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis. MAIN OUTCOME MEASURE:The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits. Because of non-proportional hazards, treatment effects are presented as life expectancy difference without failure (LEDwf), which measures the difference between average duration of survival without failure. RESULTS:Average durations of survival without failure were 19.8 months for rituximab, 15.6 months for abatacept, and 19.1 months for tocilizumab. Average durations were greater with rituximab (LEDwf 4.1, 95% confidence interval 3.1 to 5.2) and tocilizumab (3.5, 2.1 to 5.0) than with abatacept, and uncertainty about tocilizumab compared with rituximab was substantial (-0.7, -1.9 to 0.5). No evidence was found of difference between treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events. CONCLUSION:Among adults with refractory rheumatoid arthritis followed-up in routine practice, rituximab and tocilizumab were associated with greater improvements in outcomes at two years compared with abatacept.

Project description:PurposeWith the current use of biologics in rheumatoid arthritis (RA), there is a need to monitor ongoing structural joint damage due to the dissociation of articular cartilage damage from disease activity of RA. This study longitudinally analyzed levels of serum cartilage biomarkers during 54 weeks of infliximab therapy, to evaluate the feasibility of biomarkers for monitoring structural joint damage.MethodsSubjects comprised 33 patients with early RA and 33 patients with established RA. All patients received 3 mg/kg of infliximab and methotrexate for 54 weeks. Levels of the following serum cartilage markers were measured at baseline and at weeks 14, 22, and 54: hyaluronan (HA); cartilage oligometric matrix protein (COMP); type II collagen (CII)-related neoepitope (C2C); type II procollagen carboxy-propeptide (CPII); and keratin sulfate (KS). Time courses for each biomarker were assessed, and relationships between these biomarkers and clinical or radiographic parameters generally used for RA were investigated.ResultsLevels of CRP, MMP-3, DAS28-CRP, and annual progression of TSS were improved to similar degrees in both groups at week 54. HA and C2C/CPII were significantly decreased compared to baseline in the early RA group (p<0.001), whereas HA and COMP, but not C2C/CPII, were decreased in the established RA group. Strikingly, serum C2C/CPII levels were universally improved in early RA, regardless of EULAR response grade. Both ?HA and ?C2C/CPII from baseline to week 54 correlated significantly with not only ?CRP, but also ?DAS28 in early RA. Interestingly, when partial correlation coefficients were calculated by standardizing CRP levels, the significant correlation of ?HA to ?DAS28 disappeared, whereas correlations of ?C2C/CPII to ?DAS28, ?JNS, and ?HAQ remained significant. These results suggest a role of ?C2C/CPII as a marker of ongoing structural joint damage with the least association with CRP, and that irreversible cartilage damage in established RA limits restoration of the C2C/CPII level, even with tight control of joint inflammation.ConclusionThe temporal course of C2C/CPII level during anti-TNF therapy indicates that CII turnover shifts toward CII synthesis in early RA, but not in established RA, potentially due to irreversible cartilage damage. ?C2C/CPII appears to offer a useful marker reflecting ongoing structural joint damage, dissociated from inflammatory indices such as CRP and MMP-3.

Project description:Objectives: To assess whether the histopathological features of the synovium before starting treatment with the TNFi certolizumab-pegol could predict clinical outcome and examine the modulation of histopathology by treatment. Methods: Thirty-seven RA patients fulfilling UK NICE guidelines for biologic therapy were enrolled at Barts Health NHS trust and underwent synovial sampling of an actively inflamed joint using ultrasound-guided needle biopsy before commencing certolizumab-pegol and after 12-weeks. At 12-weeks, patients were categorized as responders if they had a DAS28 fall >1.2. A minimum of 6 samples was collected for histological analysis. Based on H&E and immunohistochemistry (IHC) staining for CD3 (T cells), CD20 (B cells), CD138 (plasma cells), and CD68 (macrophages) patients were categorized into three distinct synovial pathotypes (lympho-myeloid, diffuse-myeloid, and pauci-immune). Results: At baseline, as per inclusion criteria, DAS28 mean was 6.4 ± 0.9. 94.6% of the synovial tissue was retrieved from the wrist or a metacarpophalangeal joint. Histological pathotypes were distributed as follows: 58% lympho-myeloid, 19.4% diffuse-myeloid, and 22.6% pauci-immune. Patients with a pauci-immune pathotype had lower levels of CRP but higher VAS fatigue compared to lympho- and diffuse-myeloid. Based on DAS28 fall >1.2, 67.6% of patients were deemed as responders and 32.4% as non-responders. However, by categorizing patients according to the baseline synovial pathotype, we demonstrated that a significantly higher number of patients with a lympho-myeloid and diffuse-myeloid pathotype in comparison with pauci-immune pathotype [83.3% (15/18), 83.3 % (5/6) vs. 28.6% (2/7), p = 0.022) achieved clinical response to certolizumab-pegol. Furthermore, we observed a significantly higher level of post-treatment tender joint count and VAS scores for pain, fatigue and global health in pauci-immune in comparison with lympho- and diffuse-myeloid patients but no differences in the number of swollen joints, ESR and CRP. Finally, we confirmed a significant fall in the number of CD68+ sublining macrophages post-treatment in responders and a correlation between the reduction in the CD20+ B-cells score and the improvement in the DAS28 at 12-weeks. Conclusions: The analysis of the synovial histopathology may be a helpful tool to identify among clinically indistinguishable patients those with lower probability of response to TNF?-blockade.

Project description:IntroductionThe PrismRA® test identifies rheumatoid arthritis (RA) patients who are unlikely to respond to anti-tumor necrosis factor (anti-TNF) therapies. This study evaluated the clinical and financial outcomes of incorporating PrismRA into routine clinical care of RA patients.MethodsA decision-analytic model was created to evaluate clinical and economic outcomes in the 12-month period following first biologic treatment. Two treatment strategies were compared: (1) observed clinical decision-making based on a 175-patient cohort receiving an anti-TNF therapy as their first biologic after failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and (2) modeled clinical decision-making of the same population using PrismRA results to inform first-line biologic treatment choice. Modeled costs include biologic drug pharmacy, non-biologic pharmacy, and total medical costs. The odds of inadequate response to anti-TNF therapies and various components of patient care were calculated based on PrismRA results.ResultsIdentifying predicted inadequate responders to anti-TNF therapies resulted in a modeled 38% increase in ACR50 response to first-line biologic therapies. The fraction of patients who achieved an ACR50 response to any therapy (TNFi and others) within the 12-month period was 33% higher in the PrismRA-stratified population than in the unstratified population (59 vs. 44%, respectively). When therapy prescriptions were modeled according to PrismRA results, cost savings were modeled for all financial variables: overall costs (4% decreased total, 19% decreased on ineffective treatments), total biologic drug pharmacy (4% total, 23% ineffective), non-biologic pharmacy (2% total, 19% ineffective), and medical costs (6% total, 19% ineffective). Female sex was the clinical metric that showed the greatest association with inadequate response to anti-TNF therapies (odds ratio 2.42, 95% confidence interval 1.20, 4.88).ConclusionsIf PrismRA is implemented into routine clinical care as modeled, predicting which RA patients will have an inadequate response to anti-TNF therapies could save > $7 million in overall ineffective healthcare costs per 1000 patients tested and increase targeted DMARD response rates in RA.

Project description:OBJECTIVE:Phase III clinical trials of the tumour necrosis factor inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. METHODS:Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS >?0); 3 factors were selected based on strongest Pearson's correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. RESULTS:A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson's correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P?<?0.001). CONCLUSIONS:In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. CLINICAL TRIAL REGISTRATION NUMBERS:EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results.

Dataset Information

Evolution of radiographic joint damage in rituximab-treated versus TNF-treated rheumatoid arthritis cases with inadequate response to TNF antagonists.

Background

Objective

Methods

Results

Conclusion

Publications

Evolution of radiographic joint damage in rituximab-treated versus TNF-treated rheumatoid arthritis cases with inadequate response to TNF antagonists.

Similar Datasets

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